GeneCology Research Centre, The University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Qld, 4556, Australia.
Hum Genomics. 2018 Jun 28;12(1):33. doi: 10.1186/s40246-018-0166-2.
Previous studies showed that the magnitude of selection pressure in constitutive exons is higher than that in alternatively spliced exons. The intensity of selection was also shown to be depended on the inclusion level of exons: the number of transcripts that include an exon. Here, we examined how the difference in selection pressure influences the patterns of clinical variants in human exons. Our analysis revealed a positive relationship between exon inclusion level and the abundance of pathogenic variants. The proportion of pathogenic variants in the exons that are included in > 10 transcripts was 6.8 times higher than those in the exons included in only one transcript. This suggests that the mutations occurring in the exons included in multiple transcripts are more deleterious than those present in the exons included in one transcript. The findings of this study highlight that the exon inclusion level could be used to predict the mutations associated with diseases.
先前的研究表明，组成性外显子中的选择压力幅度高于选择性剪接外显子。选择的强度还取决于外显子的包含水平：包含外显子的转录本数量。在这里，我们研究了选择压力的差异如何影响人类外显子中临床变异的模式。我们的分析揭示了外显子包含水平与致病性变异体丰度之间存在正相关关系。在包含>10 个转录本的外显子中，致病性变异体的比例比仅包含一个转录本的外显子高 6.8 倍。这表明，在包含多个转录本的外显子中发生的突变比在包含一个转录本的外显子中发生的突变更具破坏性。本研究的结果强调，外显子包含水平可用于预测与疾病相关的突变。
